Partial Response Rate Research Articles

SURG-39. LONG-TERM RESULTS OF INTERVENTION FOR GROWING INCIDENTAL MENINGIOMAS OR CONTINUED ACTIVE SURVEILLANCE, A PROSPECTIVE COHORT STUDY

Abstract Incidental meningiomas are common findings. They represent a clinically challenging cohort, without a detailed consensus on their management. The risk of tumor progression and that of intervention must be considered. Long-term prospective data on incidental meningiomas are sparse. We aimed to evaluate the long-term effect of Gamma Knife Radiosurgery (GKRS), surgical resection and continued observation for growing incidental meningiomas. A prospective database of 62 patients (70 tumors) commenced under active surveillance was established in 2009. Radiological and clinical data was obtained until sept 2023. The results of long-term observation (group 1) and intervention with GKRS (group 2) or surgery (group 3) at progression was analyzed. Due to growth, 41 (58.6%) tumors were treated. The mean growth rate was higher prior to GKRS (2.1 cm 3 /y) and surgery (0.4 cm 3 /y) than during long-term active surveillance (0.009 cm 3 /y) (p < 0.001). The meningiomas became in mean 31.3% and 99.1% smaller after GKRS and resection, respectively. In comparison, tumors under long-term surveillance increased in mean 27.2% (p < 0.001). According to the RANO response criteria, the complete, partial, and minimal response versus stable disease rates were higher following intervention, the overall progressive disease rates were similar (Group 1; 20.7%, group 2: 11.4% and group 3: 16.7%) (p = 0.232). Treatment versus no-treatment did not affect overall survival (Group 1; 10.3 y, group 2: 11.8 y and group 3: 13.5 y (p = 0.264). No symptom development was registered in group 1. In group 2, 2.9% experienced transient (grade 2) adverse events, and in group 3, 50% suffered permanent (grade 4) adverse events according to the Common Terminology Criteria for Adverse Events (CTCEAv5). Intervention reduces tumor volume; however, the clinical significance remains uncertain and side effects are not negligible. Active surveillance is safe, saves > 40% of patients from unnecessary interventions and does not compromise future treatments. The optimal timing of intervention should be further explored.

Intermediate results of efficacy and safety of combined treatment with brentuximab vedotin and bendamustine for refractory and relapsed forms of peripheral T-cell lymphoma: A retrospective study

Aim. To evaluate the efficacy and safety profile of the BvB combination in the treatment of R/R nPTCL, the complete response (CR) and partial response (PR) rates, overall survival (OS), and progression-free survival (PFS). Materials and methods. The analysis included 39 patients with R/R forms of nPTCL who underwent treatment in state budgetary institutions of the Moscow Department of Health (06.2008–08.2024). The efficacy (CR, PR, OS, PFS) and safety profile of the BvB combination were evaluated. Results. The best efficacy was noted when the BvB regimen was prescribed as a 2nd-line therapy compared to 3rd and subsequent lines. The overall response rate (ORR) when prescribed as 2nd-line therapy was 57% (n=13) of cases, CR – in 39.1% (n=9), PR – in 8.7% (n=2). The use of the BvB regimen as 3rd and subsequent lines of therapy led to ORR in 5 (31.3%) patients, CR – in 2 (12.5%), PR – in 2 (12.5%) patients. Statistically significant differences were obtained for the median PFS of patients who received the BvB regimen in the 2nd vs 3rd and subsequent lines of therapy: 6.5 and 2.5 months, respectively (p=0.0304). The BvB combination was characterized by an acceptable safety profile. Conclusion. The use of the BvB regimen in R/R forms of nPTCL demonstrated high efficacy and an optimal safety profile. The obtained results indicate the need to continue the study on a larger group of patients.

Hyperbaric oxygen therapy in the treatment of late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation

Introduction: Hemorrhagic cystitis (HC) is a common complication after allogeneic hematopoietic stem cell transplantation (HSCT), characterized by inflammation and bleeding of the bladder. Hyperbaric oxygen therapy (HBOT) has been shown to be effective in the treatment of radiation-induced HC. However, the optimal treatment for HC after allogeneic HSCT has not yet been established. Furthermore, limited research has been conducted on the use of HBOT in this setting. This study aimed to evaluate the effectiveness and safety of HBOT in patients with late-onset HC after allogeneic HSCT. Methods: Twenty-five-year (1998–2022) retrospective analysis performed in all consecutive patients with confirmed late-onset HC after allogeneic HSCT treated with HBOT at two centers in Portugal. Medical records were reviewed for clinical and laboratory features, primary indications for allogeneic HSCT, conditioning regimen, and treatment strategies for HC. Patients received 100% oxygen at 2.1–2.5 atmosphere absolute pressure (ATA) for 70–90-minute periods, once daily, five times per week. Complete clinical response was defined as the absence of macroscopic hematuria sustained for at least 2 weeks, and partial response was described as a downgrading in the severity of HC. Statistical significance was considered for values of p < 0.05. Results: The sample included 61 patients with a mean age of 28.0 (SD 14.2) years, 33 males. Complete response was achieved in 72.1% (n = 44) of patients and partial response in 14.8% (n = 9). Concerning patients with a complete response, the median number of HBOT sessions was 15.5 sessions (IQR 10.0-26.8). Patients treated with 10 or more sessions of HBOT had a higher rate of complete or partial response (OR 12.5, 95%CI 1.9–83.2, p-value < 0.05). There was no response in 8 (13.1%) patients, and 6 interrupted the treatments early. Only 2 patients suspended the HBOT due to a lack of clinical benefit. Conclusion: Our study supports using of HBOT as an adjunctive treatment for late-onset HC after allogeneic HSCT. Furthermore, 10 or more HBOT sessions delivered seem to impact the rate of HC resolution. Prospective, randomized, and well-controlled trials are needed to establish HBOT’s definitive efficacy and safety.

CD27-Armored BCMA CAR T Cell Therapy (CBG-002) for Relapsed and Refractory Multiple Myeloma: A Phase I Clinical Trial.

B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cell therapy has been approved for the treatment of relapsed and refractory multiple myeloma (RRMM); however, whether patients have long-term response has yet to be established. We investigated the feasibility of CBG-002, an CD27-armored BCMA CAR T therapy, to improve clinical efficacy in patients with RRMM. We present preclinical data showing the activity of CBG-002 against myeloma and results from a phase I clinical trial (NCT04706936) evaluating its safety and efficacy in patients with RRMM. The primary endpoint was safety, as assessed by grade 3 or 4 adverse events(AEs). Key secondary endpoints were overall response rate (ORR), duration of response (DOR), progression-free survival (PFS) and overall survival (OS). A total of 11 patients were enrolled and received CBG-002 therapy. Nine patients developed grade 1 or 2 cytokine release syndrome (CRS), while no patients experienced grade 3 or higher CRS or immune effector cell-associated neurotoxicity syndrome. Other grade 3 or higher AEs included neutropenia (72.7%), thrombocytopenia (45.5%) and anemia (36.4%). At a median follow-up of 16.7 months, the ORR was 81.8%, including a stringent complete response/complete response rate of 45.5%, very good partial response rate of 18.2%, and partial response rate of 18.2%, with a median DOR of 8.9 (range 1.8-21.9) months. The median OS was not reached, and the median PFS was 8.5 (2.7-22.9) months. In this phase I study, CBG-002, a CD27-armored BCMA CAR T therapy, demonstrated safety and clinical efficacy in patients with RRMM.

Efficacy of Biofeedback Therapy for Giggle Incontinence in Children: How Many Sessions Are Required?

Giggle incontinence (GI) is characterized by the sudden and involuntary expulsion of urine coinciding with episodes of laughter. The underlying pathophysiology of this condition remains unclear, and various treatment approaches are employed. The objective of this study is to assess the effectiveness of biofeedback (BF) therapy in treating GI and ascertain the requisite number of therapy sessions needed for efficacy. Medical records of children treated with BF therapy for GI between November 2022 and November 2023 were retrospectively analyzed. The success of treatment was assessed after four and eight sessions, as well as following three maintenance sessions. Treatment outcomes were evaluated using the scoring system recommended by the International Children's Continence Society (ICCS), which categorizes responses into three levels: no response (Score 0), partial response (Score 1), and complete response (Score 2). Thirteen patients were initially diagnosed with GI. Of these, 10 patients were included in the study as three discontinued treatments. The cohort comprised an equal gender distribution with five females (50.0%) and five males (50.0%). The mean age of patients was 8.9 ± 3.3 (range 5-16) years. Two out of ten patients had a history of previous treatment for overactive bladder, while three had received treatment for primary monosymptomatic nocturnal enuresis. Following the completion of all BF sessions, the rate of complete response was observed at 80.0% (n = 8), while the partial response rate accounted for 10.0% (n = 1). Statistical analysis revealed significant differences in response scores after four and eight sessions (p < 0.01) as well as between the results after eight sessions and the completion of maintenance sessions (p < 0.01). BF therapy demonstrates a high success rate in managing GI. Completion of at least eight BF therapy sessions enhances the probability of a successful outcome in the treatment of GI. Additionally, it has been observed that maintenance sessions contribute to the increased efficacy of the treatment.

Novel intravesical therapies and delivery systems for the management of bladder cancer.

Bladder cancer is a substantial burden for public health worldwide. A risk-adapted treatment strategy is required for non muscle-invasive (NMIBC) and muscle-invasive bladder cancer (MIBC). To date, treatment includes surgery with or without peri-operative local or systemic treatment. The aim of this review was to explore novel intravesical therapies and delivery systems emerging in NMIBC and MIBC. Several novel intravesical therapies and delivery systems for NMIBC and MIBC treatment recently emerged. Hyperthermic intravesical chemotherapy (HIVEC) allows a reasonable cancer control in selected high-risk NMIBC. Novel intravesical drugs such as nadofaragene firadenovec, Oncofid-P-B or Nogapendekin alfa-inbakicept seem to be safe and well tolerated. However, their efficacy in high-risk NMIBC should be further investigated. Hydrogels appear to be safe, well tolerated and potentially efficient in primary chemoablation in selected cases of low-grade intermediate-risk NMIBC tumors. Drug-releasing intravesical systems (drug-RIS) such as TAR-200 are safe and well tolerated, providing high partial and complete response rate in both NMIBC and MIBC patients. The armamentarium for the treatment of bladder cancer patients is expanding, notably with HIVEC, hydrogels, drug-RIS and novel therapies. However, accurate patients' selection is key to prevent disease progression in any bladder-sparing strategy, and radical cystectomy remains the gold-standard to date.

12459 Exceptional Response To A Single Dose Of Pembrolizumab As Salvage Therapy In A Patient With Metastatic Adrenocortical Carcinoma (ACC)

Abstract Disclosure: L. Branchaud-Croisetière: None. J. Castilloux: None. E. Turcotte: None. A. Bégin: None. M. St-Jean: Advisory Board Member; Self; GlaxoSmithKline, HRA Pharmaceuticals. Research Investigator; Self; AstraZeneca, Novo Nordisk, Spruce Biosciences. Speaker; Self; GlaxoSmithKline, Recordati Rare Diseases. In advanced ACC, limited effective treatment options are available beyond mitotane and cytotoxic chemotherapy. PD-L1 blockade has shown promising results in small numbers of advanced ACC. In ACC, the reported partial response rate to pembrolizumab is around 25%.[1] Only one case of a significant partial response to a single dose of Pembrolizumab as salvage therapy for metastatic ACC was previously published.[1] In April 2023, a 19-year-old woman presented with severe hypertension, hypokalemia and clinical signs of Cushing syndrome (CS). Thoraco-abdominal scan revealed a left-sided cluster of confluent adrenal masses (7.3 x 14.4 x 11.4 cm), a left cortical renal lesion (2.8x2x2.1cm), a right ovarian teratoma (7.9 x 7.8x7.9 cm) and at least 25 pulmonary micronodules. FDG-PET SCAN revealed a significant hypermetabolism of the left adrenal lesions (SUV 18.6), ovarian teratoma (SUV 5.5) and pulmonary micronodules (SUV 1.1-2). Cortisol and androgens secretion was confirmed biochemically. Initially, she was not candidate for a debulking surgery because the tumor was surrounding the aorta, and mesenteric arteries. Hypertension and hypokalemia were treated with spironolactone, amlodipine, amiloride and irbesartan. Cushing syndrome was treated with metyrapone. In April 2023, Etoposide-Doxorubicine-Cisplatin (EDP) was administered in combination with Mitotane (max: 8g/day). After 6 cycles of EDP-M the disease regressed slightly but was considered stable based on RECIST criteria. After 8 cycles, the follow-up imaging showed a progression of the adrenal lesion (9.2x18.2cm) but stable pulmonary micronodules. A biopsy of the adrenal lesion, for therapeutic purpose, revealed microsatellite stability (MSS). The patient refused germinal genetic testing. It was decided in multidisciplinary tumor board to try Pembrolizumab. In December 2023, she received one cycle of Pembrolizumab (140mg), but the treatment was complicated by grade 4 immune-mediated hepatitis. A few weeks following Pembrolizumab she completely normalized her blood pressure and hypokalemia despite cessation of all her anti-hypertensive drugs. Pembrolizumab and Mitotane were stopped and hepatitis completely resolved after two months of Mycophenolate Mofetil and ongoing decreasing dose of prednisone. In March 2024, CT scan showed a 60% regression of the adrenal mass (4.1 x 7.2 cm), stability of the renal lesion and ovarian teratoma and complete resolution of the pulmonary micronodules. We suspect an ongoing effect of immunotherapy and Mitotane, since Mitotane levels were still in the therapeutic range (15.1 mg/L) six weeks following cessation. Mitotane was resumed in March 2024. The patient will potentially have a resection of the left adrenal lesion in the next month. This is second published case of a significant response to Pembrolizumab as second-line therapy for advanced ACC. [1] Raj Net al. J Clin Oncol. 2020 Presentation: 6/1/2024

Immune checkpoint inhibitors with or without radiotherapy in metastatic non‑small cell lung cancer: A meta‑analysis and literature review.

The combination of immune checkpoint inhibitors (ICIs) and radiotherapy has shown promise in the treatment of metastatic non-small cell lung cancer (NSCLC). The present meta-analysis aimed to determine the efficacy and safety of combining radiotherapy (RT) ICIs for the treatment of metastatic NSCLC. PubMed, Google Scholar, the Cochrane Library and Web of Science databases were searched for relevant articles up to February 1, 2023. Post-therapy outcomes such as progression-free survival (PFS), complete response, partial response (PR), progressive disease (PD), stable disease and adverse events (AEs) were analyzed. The meta-analysis was performed using RevMan 5.4 software. A total of seven studies involving 682 patients were included (384 patients who received ICI + RT vs. RT and 298 patients who received ICI + RT vs. ICI alone). No significant difference in PFS was demonstrated between the ICI + RT group and the RT group (heterogeneity: χ2=2.35; df=1; P=0.13; I2=57% and test for overall effect: Z=0.10; P=0.92). Conversely, patients in the ICI alone group had significantly decreased PR rates (heterogeneity: Τ2=0.00; χ2=2.13; df=3; P=0.54; I2=0% and test for overall effect: Z=2.57; P=0.01) compared with patients in the ICI + RT group. The ICI + RT group also had significantly lower rates of PD (heterogeneity: Τ2=0.00; χ2=0.91; df=3; P=0.82; I2=0% and test for overall effect: Z=2.52; P=0.01) compared with the ICI alone group. Safety analysis revealed no significant difference between patients who received ICI + RT and those who received RT in terms of grade 1 or 2 AEs. In conclusion, the combination of ICIs + RT demonstrates promising efficacy and safety for patients with metastatic NSCLC. However, clinical trials that have tested this combination are lacking, which emphasizes the need for further research.

Repeated subcutaneous esketamine on treatment-resistant depression: An open-label dose titration study

BackgroundKetamine has recently gained prominence as one of the most effective therapeutic options in unipolar treatment-resistant depression (TRD). However, most studies related to the antidepressant action of ketamine used intravenous (IV) or intranasal (IN) administration. The subcutaneous (SC) route of administration is a promising alternative, as it results in plasma levels comparable to IV, causes fewer side effects, and is easier and cheaper to administer than both IV and IN routes. MethodsIn this context, we conducted an open-label clinical trial for investigating the efficacy and safety of 8 weekly sessions of SC esketamine in TRD patients (n = 30). ResultsAt the end of the treatment, a partial response rate of 26.09 %, a response rate of 52.17 % and remission rate of 34.78 % were observed. The self-reported depressive symptoms, as measured by the Beck Depression Inventory II, significantly decreased from the baseline to the final session, and the improvements were sustained throughout the week. Follow-up evaluations up to the sixth month consistently showed scores lower than the baseline. LimitationsThe small sample size and the drop-out during the follow-up phase may limit the generalizability of the findings. Additionally, the absence of a control group necessitates cautious interpretation of causality. ConclusionsThis pioneering study, which addresses SC esketamine treatment for TRD, reported promising response and remission rates, as well as sustained effects. It highlights the need for further research to improve and expand our knowledge of this innovative, more accessible, and cost-effective therapeutic approach.

Absolute lymphocyte count predicts efficacy of palbociclib in patients with metastatic luminal breast cancer

BackgroundAbsolute lymphocyte count (ALC) is a predictive and prognostic factor for various tumor types, including breast cancer. Palbociclib is a CDK4/6 inhibitor widely used for the treatment of metastatic estrogen receptor (ER)-positive, HER2-negative breast cancer. However, predictive biomarkers of the efficacy of palbociclib remain unelucidated. We conducted a retrospective study to examine the predictive value of the baseline ALC in patients treated with palbociclib.MethodsThe medical records of patients with ER-positive, HER2-negative breast cancer treated with palbociclib plus hormonal therapy between December 2017 and December 2021 were analyzed retrospectively. The cutoff value of ALC was set at 1800 cells/μL at the initiation of palbociclib treatment. The clinical benefit rate (CBR) was defined as the rate of complete or partial response or stable disease for at least 6 months. Progression-free survival (PFS) rates were estimated using the Kaplan–Meier method and compared using the log-rank test. Univariate and multivariate analyses were performed using Cox proportional hazards regression.ResultsAll of the 202 patients were women, with a median age of 59 years and a performance status (PS) of ≤ 2. The median numbers of lines of chemotherapy and endocrine therapy before palbociclib treatment were 0 (range, 0–9) and 1 (range, 0–7), respectively. Fifty-one patients had liver metastases. Forty-six patients tested negative for progesterone receptor (PgR) expression. The median follow-up time was 9.1 months. The CBR was significantly higher in the ALC-high group than in the ALC-low group (79% vs. 60%; P = 0.018). The median PFS was significantly longer in the ALC-high group than in the ALC-low group (26.8 months vs. 8.4 moths, respectively; P = 0.000013). ALC, age, PS, PgR status, prior chemotherapy, prior endocrine therapy, and liver metastasis were entered into the multivariate analysis. ALC was identified as an independent factor for PFS (P = 0.00085), along with liver metastasis (P = 0.0020), PS (P = 0.026), and prior endocrine therapy (P = 0.019).ConclusionALC can serve as a predictor of palbociclib efficacy in patients with metastatic ER-positive, HER2-negative breast cancer.

Belantamab mafodotin, pomalidomide, and dexamethasone for triple class exposed/refractory relapsed multiple myeloma: a subgroup analysis of the ALGONQUIN trial

Given the early use of triplet and quadruplet regimens, most patients with multiple myeloma (MM) will be exposed and/or refractory to PIs, IMiDs, and anti-CD38 mAbs after first- or second-line treatment. Effective treatment for this group of triple class exposed/refractory (TCE/R) patients is crucial. Here we present a post-hoc subgroup analysis of TCE/R patients treated on the ALGONQUIN study of belantamab mafodotin plus pomalidomide-dexamethasone (belamaf-Pd) for relapsed MM. Of the 99 patients treated on the ALGONQUIN study, 69 were TCE and 56 were TCR and were included in this analysis. Patients had a median of three prior lines of therapy. The ORR was 86.4% in TCE patients and 84.9% in TCR patients, with ≥ very good partial response rates of 64% and 68% respectively. The median progression free survival was 18.3 months in TCE patients and 19.6 months in TCR patients, with overall survival not yet reached and 34.4 months, respectively for TCE and TCR patients. No new safety signals were identified. The most common Grade ≥ 3 AEs were keratopathy (48%), decreased visual acuity (42%), neutropenia (36%), thrombocytopenia (27%), and infection (25%). In this subgroup analysis of the ALGONQUIN study, patients with TCE/TCR disease treated with belamaf-Pd achieved high clinical response rates with durable remissions, comparable to other novel therapeutics in this space.

The clinical utility of autologous tumor lysate-loaded dendritic cell vaccination for patients with glioma: A systematic review and meta-analysis.

Dendritic cell (DC) vaccines show promise for glioma treatment, but optimal use remains uncertain. This meta-analysis examined DC vaccine efficacy and safety for gliomas. This systematic review and meta-analysis study was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. From the date of inception to October 23, 2023, electronic databases PubMed, Embase, Web of Science, and Scopus have been thoroughly evaluated. A total of 12 studies with 998 patients and a mean age ranging from 40.2 to 56 years were included. Across 12 articles, DC vaccine 6-month overall survival (OS) was 100% [95% confidence interval {95%CI}: 100%-100%]. Respectively, 12-month OS reported 75% [95%CI: 65%-85%] but declined to 32% [95%CI: 20%-43%] for 24-month OS. 6- and 12-month progression-free survival reached 49% [95%CI: 21%-77%] and 19% [95%CI:8%-30%]. Studying radiological outcomes shows that complete response and partial response rates were 13% [95%CI: 17%-42%], and 26% [95%CI: 10%-42%], though stable disease reached 33% [95%CI: 15%-51%], suggesting predominant antineoplastic effects. The progressive disease rate also was 24% [95%CI: 9%-57%]. In gliomas, DC vaccinations show a temporary efficacy; stability is more prevalent than regression. Impacts favor decreased resistance to early disease. Enhancing efficacy remains critical. Early therapy can be enhanced by appropriate supplementary therapy integration.

Efficacy of CARVYKTI in CARTITUDE-4 versus other conventional treatment regimens for lenalidomide-refractory multiple myeloma using inverse probability of treatment weighting.

Aim: The phase III randomized controlled trial (RCT) CARTITUDE-4 (NCT04181827) demonstrated superiority of CARVYKTI (ciltacabtagene autoleucel; cilta-cel) over daratumumab, pomalidomide and dexamethasone (DPd) and pomalidomide, bortezomib and dexamethasone (PVd) for relapsed/refractory multiple myeloma (RRMM) patients who have received one to three prior line(s) of therapy (LOT[s]) including an immunomodulatory agent and a proteasome inhibitor, and are refractory to lenalidomide. These analyses estimate the relative efficacy between cilta-cel and other common treatment regimens, for which no direct comparative evidence is available. Materials & methods: Patient data were available from the CARTITUDE-4, CASTOR, CANDOR and APOLLO RCTs. Imbalances between cohorts on key patient characteristics were adjusted for using inverse probability of treatment weighting (IPTW). Relative efficacies were estimated with response rate ratios (RRs) and 95% confidence intervals (CIs) for overall response rate (ORR), very good partial response or better rate (≥VGPR) and complete response or better rate (≥CR), and with hazard ratios (HRs) and 95% CIs for progression-free survival (PFS). Sensitivity analyses using different analytical methods and additional covariates were explored. Results: Key characteristics were well balanced across cohorts after IPTW. Cilta-cel showed statistically significant benefit in PFS (HRs: 0.11-0.51), ≥VGPR (RRs: 1.51-5.13) and ≥CR (RRs: 2.90-35.24) versus all comparators, and statistically significant improvements in ORR over most comparator regimens (RRs: 1.22-1.90). Results were consistent across sensitivity analyses. Conclusion: Cilta-cel demonstrated benefit over other common treatment regimens, highlighting its potential to become a new standard of care option for lenalidomide-refractory RRMM patients with one to three prior LOT(s). These comparisons help to demonstrate the improved efficacy of cilta-cel in countries where the standard of care may differ from DPd/PVd.

Efficacy and safety of intravenous ketamine treatment in Japanese patients with treatment-resistant depression: A double-blind, randomized, placebo-controlled trial.

Although the antidepressant effect of ketamine on treatment-resistant depression (TRD) has been frequently reported in North American and European countries, evidence is scarce among the Asian population. We aimed to evaluate the efficacy and safety of intravenous ketamine in Japanese patients with TRD. In this double-blind randomized placebo-controlled trial, 34 Japanese patients with TRD were randomized to receive either intravenous ketamine (0.5 mg/kg) or placebo, administered over 40 min, twice a week, for 2 weeks. The primary outcome was the change in the Montgomery Åsberg Depression Rating Scale (MADRS) total score from baseline to post-treatment. Secondary outcomes included changes in other depressive symptomatology scores and remission, response, and partial response rates. We also examined the association between baseline clinical demographic characteristics and changes in the MADRS total score. Intention-to-treat analysis indicated no significant difference in the decrease in MADRS total score between the groups (-8.1 ± 10.0 vs -2.5 ± 5.2, t[32] = 2.02, P = 0.052), whereas per-protocol analysis showed a significant reduction in the ketamine group compared to the placebo group (-9.1 ± 10.2 vs -2.7 ± 5.3, t[29] = 2.22, P = 0.034). No significant group differences were observed in other outcomes. Adverse events were more frequent in the ketamine group than in the placebo group, and no serious adverse events were reported. A higher baseline MADRS total score and body mass index were associated with a greater reduction in the MADRS total score. Intravenous ketamine outperformed placebo in Japanese patients with TRD who completed the study, suggesting that ketamine could alleviate depressive symptoms of TRD across diverse ethnic populations.

Safety and efficacy of B cell maturation antigen-directed CAR T-cell therapy in patients with relapsed/refractory multiple myeloma and concurrent light chain amyloidosis.

Clinical trials evaluating chimeric antigen receptor (CAR) T-cell therapy in relapsed/refractory multiple myeloma (RRMM) have typically excluded patients with AL amyloidosis. As a result, there are limited data on the safety and efficacy of CAR T-cell therapy in this patient population. We retrospectively reviewed eight consecutive patients with RRMM and AL amyloidosis who were treated with standard of care CAR T-cell therapy. Cytokine release syndrome was seen in 75% of patients (grade ≥3: 0%) and immune effector cell-associated neurotoxicity syndrome (grade 1) in only one patient. Low-grade cytopenias were common (any grade/grade ≥3: neutropenia 62.5%/37.5%, anemia 37.5%/0%, thrombocytopenia 25%/0%). CAR T-cell therapy led to rapid and deep responses with a median time to best response of 43 days and a hematologic very good partial response or better rate of 62.5%. Overall, we found that commercial CAR T-cell therapy was feasible, and effective in patients with RRMM and concurrent AL amyloidosis.

Early intervention with oral mucosal barrier Protective agents in chronic oral graft-versus-host disease: a retrospective cohort study

BackgroundPreventing the progression of chronic oral graft-versus-host disease (cGVHD) is essential for maintaining oral health, improving quality of life, minimizing functional impairment, reducing systemic complications, and addressing treatment challenges.PurposeTo evaluate the effectiveness of early intervention with oral mucosal barrier protective agents in preventing the progression of cGVHD and its impact on oral health, quality of life, and treatment response.MethodsThis retrospective cohort study included 75 participants, with 34 in the non-oral mucosal barrier protective agent group and 41 in the oral mucosal barrier protective agent group. Baseline characteristics, oral mucosal health parameters, quality of life assessments, and curative effect data were collected and compared between the two study groups.ResultsThe group receiving oral mucosal barrier protectants (n = 41) exhibited significantly lower severity of oral mucositis compared to the group without such protectants (n = 34) (2.12 ± 0.48 vs. 2.56 ± 0.63, P = 0.001) and the incidence of complications was significantly lower in the group receiving oral mucosal barrier protectants (P < 0.05). Additionally, the quality of life assessment showed marked improvements in somatization, emotional management, and social reintegration in the oral mucosal barrier protectant group compared to the group without these protectants (P < 0.05). Furthermore, the assessment of treatment efficacy revealed significantly higher rates of both complete and partial responses in the oral mucosal barrier protectant group, along with a notable reduction in disease progression compared to the group without these protectants (P < 0.001).ConclusionEarly intervention with oral mucosal barrier protective agents was associated with improved oral health parameters, enhanced quality of life, and a more favorable treatment response in the context of cGVHD.

Efficacy of hepatic arterial infusion chemotherapy and its combination strategies for advanced hepatocellular carcinoma: A network meta-analysis

BACKGROUND With the rapid progress of systematic therapy for hepatocellular carcinoma (HCC), therapeutic strategies combining hepatic arterial infusion chemotherapy (HAIC) with systematic therapy arised increasing concentrations. However, there have been no systematic review comparing HAIC and its combination strategies in the first-line treatment for advanced HCC. AIM To investigate the efficacy and safety of HAIC and its combination therapies for advanced HCC. METHODS A network meta-analysis was performed by including 9 randomized controlled trails and 35 cohort studies to carry out our study. The outcomes of interest comprised overall survival (OS), progression-free survival (PFS), tumor response and adverse events. Hazard ratios (HR) and odds ratios (OR) with a 95% confidence interval (CI) were calculated and agents were ranked based on their ranking probability. RESULTS HAIC outperformed Sorafenib (HR = 0.55, 95%CI: 0.42-0.72; HR = 0.51, 95%CI: 0.33-0.78; OR = 2.86, 95%CI: 1.37-5.98; OR = 5.45, 95%CI: 3.57-8.30; OR = 7.15, 95%CI: 4.06-12.58; OR = 2.89, 95%CI: 1.99-4.19; OR = 0.48, 95%CI: 0.25-0.92, respectively) and transarterial chemoembolization (TACE) (HR = 0.50, 95%CI: 0.33-0.75; HR = 0.62, 95%CI: 0.39-0.98; OR = 3.08, 95%CI: 1.36-6.98; OR = 2.07, 95%CI: 1.54-2.80; OR = 3.16, 95%CI: 1.71-5.85; OR = 2.67, 95%CI: 1.59-4.50; OR = 0.16, 95%CI: 0.05-0.54, respectively) in terms of efficacy and safety. HAIC + lenvatinib + ablation, HAIC + ablation, HAIC + anti- programmed cell death 1 (PD-1), and HAIC + radiotherapy had the higher likelihood of providing better OS and PFS outcomes compared to HAIC alone. HAIC + TACE + S-1, HAIC + lenvatinib, HAIC + PD-1, HAIC + TACE, and HAIC + sorafenib had the higher likelihood of providing better partial response and objective response rate outcomes compared to HAIC. HAIC + PD-1, HAIC + TACE + S-1 and HAIC + TACE had the higher likelihood of providing better complete response and disease control rate outcomes compared to HAIC alone. CONCLUSION HAIC proved more effective and safer than sorafenib and TACE. Furthermore, combined with other interventions, HAIC showed improved efficacy over HAIC monotherapy according to the treatment ranking analysis.

Chidamide plus R-GDP for relapsed/refractory diffuse large B-cell lymphoma in patients ineligible for autologous transplantation: A prospective, single-arm, phase II study.

In relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), a negative prognosis is frequently linked to heightened epigenetic heterogeneity. Chidamide, a selective histone deacetylase inhibitor, shows promise as a targeted therapy for R/R DLBCL by targeting abnormal epigenetic changes associated with poor prognosis. A cohort of 27 ineligible patients with R/R DLBCL participated in an open - label, single - arm study. Chidamide was administered orally at a dose of 30 mg twice weekly for one week during the induction monotherapy phase. The subsequent combination therapy phase involved oral chidamide at a dose of 20 mg twice weekly for two weeks, followed by a one-week discontinuation period, in conjunction with intravenous R-GDP every 21 days. Among the cohort of 31 patients who underwent screening (median age: 67 years), 27 were ultimately included in the study, with 14 individuals successfully completing six cycles of C-R-GDP treatment. The overall best objective response rate was determined to be 79.1% (95% CI: 75.1%-83.3%), comprising a complete response rate of 45.8% (95% CI: 41.6%-49.9%) and a partial response rate of 33.3% (95% CI: 29.3%-37.4%). Within the subgroup of 14 patients who completed the full treatment regimen, the best objective response rate reached 100%, with 71.4% achieving complete response (n = 10) and 28.6% achieving partial response (n = 4). The median follow-up period for these patients was 17.0 months, ranging from 3.5 to 55 months. Progression-free survival was 5.9 months and overall survival was 48.3 months. Anemia was the most common adverse event, affecting all patients. Thrombocytopenia led to treatment interruption or dose reduction in 13 patients. Other common adverse events included hypocalcemia, hyponatremia, and hypokalemia. Three patients experienced grade 3 pneumonitis and one had grade 3 skin rash. Chidamide combined with R-GDP is a safe and effective treatment option for patients with R/R DLBCL who are not eligible for autologous stem cell transplantation.

Systemic therapies and primary tumour downsizing in renal cell carcinoma: a real-world comparison of anti-angiogenic and immune checkpoint inhibition regimens.

To investigate responses in the primary tumour to different systemic treatment regimens in patients with metastatic renal cell carcinoma (mRCC). A single-centre retrospective analysis of treatment-naive mRCC patients without prior nephrectomy receiving VEGF tyrosine kinase inhibitors (VEGF only), immune checkpoint inhibitors (IO only), or combinations thereof (IO + VEGF). The primary outcome was the rate of partial response in the primary tumour (primary tumour PR, ≥ 30% diameter reduction). Secondary outcomes were time to best primary tumour diameter change, overall survival (OS) and progression-free survival (PFS) by Kaplan-Meier analysis. Predictors of survival outcomes were explored by Cox proportional hazards regression analysis. The rate of primary tumour PR was 14% for VEGF only (4/28 patients), 22% for IO only (5/23) and 50% for IO + VEGF (7/14), with median best primary tumour diameter change of -8.0%, + 5.1%, and -31.1% respectively, and median time to best primary tumour diameter change of 3.2, 3.0 and 6.9months respectively. Median OS was significantly greater with IO + VEGF compared to VEGF only (HR 0.45, p = 0.04) and non-significantly greater compared to IO only (HR 0.46, p = 0.06). In multivariable analysis, primary tumour PR was the only response variable significantly associated with both OS (adjusted HR 0.32, p = 0.01) and PFS (adjusted HR 0.29, p < 0.01). mRCC patients without prior nephrectomy receiving first-line IO + VEGF regimens showed the greatest primary tumour responses, suggesting further prospective evaluation of this combination in the neoadjuvant and deferred cytoreductive nephrectomy settings.

Antibiotics are associated with worse outcomes in lung cancer patients treated with chemotherapy and immunotherapy

Anti-PD(L)-1 inhibition combined with platinum doublet chemotherapy (Chemo-IO) has become the most frequently used standard of care regimen in patients with non-small cell lung cancer (NSCLC). The negative impact of antibiotics on clinical outcomes prior to anti-PD(L)-1 inhibition monotherapy (IO) has been demonstrated in multiple studies, but the impact of antibiotic exposure prior to initiation of Chemo-IO is controversial. We assessed antibiotic exposures at two time windows: within 60 days prior to therapy (-60 d window) and within 60 days prior to therapy and 42 days after therapy (-60 + 42d window) in 2028 patients with advanced NSCLC treated with Chemo-IO and IO monotherapy focusing on objective response rate (ORR: rate of partial response and complete response), progression-free survival (PFS), and overall survival (OS). We also assessed impact of antibiotic exposure in an independent cohort of 53 patients. Univariable and multivariable analyses were conducted along with a meta-analysis from similar studies. For the -60 d window, in the Chemo-IO group (N = 769), 183 (24%) patients received antibiotics. Antibiotic exposure was associated with worse ORR (27% vs 40%, p = 0.001), shorter PFS (3.9 months vs. 5.9 months, hazard ratio [HR] 1.35, 95%CI 1.1,1.6, p = 0.0012), as well as shorter OS (10 months vs. 15 months, HR 1.50, 95%CI 1.2,1.8, p = 0.00014). After adjusting for known prognostic factors in NSCLC, antibiotic exposure was independently associated with worse PFS (HR 1.39, 95%CI 1.35,1.7, p = 0.002) and OS (HR 1.61, 95%CI 1.28,2.03, p < 0.001). Similar results were obtained in the -60 + 42d window, and also in an independent cohort. In a meta-analysis of patients with NSCLC treated with Chemo-IO (N = 4) or IO monotherapy (N = 13 studies) antibiotic exposure before treatment was associated with worse OS among all patients (n = 11,351) (HR 1.93, 95% CI 1.52, 2.45) and Chemo-IO-treated patients (n = 1201) (HR 1.54, 95% CI 1.28, 1.84). Thus, antibiotics exposure prior to Chemo-IO is common and associated with worse outcomes, even after adjusting for other factors. These results highlight the need to implement antibiotic stewardship in routine oncology practice.